New retinoid chemotypes: 9-cis-retinoic acid analogs with hydrophobic rings derived from terpenes as selective RAR agonists.
A series of 9-cis-retinoic acid analogs modified at the hydrophobic ring with a (bi)cyclohexenyl moiety derived from natural terpenes has been stereoselectively prepared using a Suzuki cross-coupling as key step. Transient transactivation studies indicate that modification of the hydrophobic ring impacts dramatically on RXR-binding and transactivation, with most retinoids being inactive on RXRbeta, while preserving their RAR pan-agonist profile. Furthermore, only the RARgamma subtype was capable of enantiomeric discrimination with some pairs of enantiomeric terpene-retinoids.
Alvarez
Susana
S
Departamento de Química Orgánica, Universidade de Vigo, 36310 Vigo, Spain.
Pazos-Randulfe
Yolanda
Y
Khanwalkar
Harshal
H
Germain
Pierre
P
Alvarez
Rosana
R
Gronemeyer
Hinrich
H
de Lera
Angel R
AR
D000077556:Alitretinoin; D057927:Hydrophobic and Hydrophilic Interactions; D018168:Receptors, Retinoic Acid / Q000819:agonists*; D047488:Retinoid X Receptors / Q000819:agonists*; D013237:Stereoisomerism; D013729:Terpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014212:Tretinoin / Q000737:chemistry*
D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D013729:Terpenes; D000077556:Alitretinoin; D014212:Tretinoin